Protein levels of APP, ADAM10 and BACE1 in aging adults with Down syndrome: Preliminary findings

Abstract

AbstractBackgroundDown syndrome (DS) is associated with high prevalence of dementia, with onset in late adulthood. Given the pathological similarities, dementia in DS is regarded as a variant of early‐onset Alzheimer’s disease (AD). The genetic causality of dementia in DS is attributed to the overexpression of the amyloid precursor protein (APP) gene located on chromosome 21. Abnormalities in the regulation of APP metabolism cause the overproduction of the amyloid‐beta peptide (Aβ) and subsequent effects on the amyloid cascade, which ultimately lead to the formation of neuritic plaques and neurofibrillary tangles. To compare protein levels of secreted APP metabolites (sAPP) and APP‐secretases (ADAM10, BACE1, PSEN1) in platelets from adults and elders with DS compared to controls, and to determine whether these findings correlate with global cognitive state.MethodThe study group comprises 21 aging adults with DS, and the comparison group comprises a similar number of age/gender‐matched healthy subjects with normal karyotype (controls). DS subjects were subdivided according to age stratification (20‐34 years, n=8; 35‐49 years, n=4; ≥50 years, n=9). Global cognitive state of participants was ascertained with the CAMCOG schedule (controls) or its adapted version for DS (CAMCOG‐DS). Protein levels of APP‐related biomarkers were determined by Western Blotting.ResultCAMCOG‐DS scores were significantly different in DS subgroups (clinical evidence of cognitive impairment/dementia, DSd; normal cognitive function, DSnc). DSd subjects achieving lower scores (43.8, SD20.7) than DSnc (66.4, SD16.1) p=0.001. Low levels of APP130 have been found among DS as age increased (1.71, SD0.99; 0.76, SD0.46; 0.48, SD0.16, respectively; p=0,013), and higher BACE1 levels was found between aged 35‐49 years old DS (0.44, SD0.77) compared with aged 20‐34 years old DS (0.70, DS0.20), p=0,048. No statistically significant differences were found in platelet levels of ADAM10.ConclusionIn this preliminary analysis, APP‐related platelet biomarkers was able to show significant differences among DS age groups.